No Surgery Trial / Two Dose-escalation Strategies (Morpheus)

A Phase III Study Testing Two Dose Escalation Strategies to Increase the Population of Complete Responders After Radiation Therapy in the Context of Organ Preservation for Patients With Rectal Cancer

A randomized study of 145 patients. Patients with a clinical T2-3 N0 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions).

It is becoming clear that there is a now an international consensus that rectal cancer research efforts need to be more focused in optimizing a non-surgical approach. This concept is very relevant to an ageing patient population with multiple co-morbidities regularly seen at the Jewish General Hospital and across the province. After interim analysis on 40 patients of the pilot study a phase III study is proposed. We are therefore proposing a phase III multicentric study of 145 patients to compare the two best known radiation dose escalation strategies and to achieve a complete clinical response. Patients with a clinical T2-3 N0-1 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions). Patients that have a high risk of recurrence or with more advanced stages of the disease will be excluded from the study, as only the local disease is being treated. The primary outcome for this proposal is rectum preservation in treated patients.

standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy in 5; Complete responders and Non-complete responders

standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions; Complete responders and Non-complete responders

Patients that are complete responders will not have surgery. Patients that are non-complete responders will have surgery.

45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions

The time between the date of randomization and recurrence, either in the pelvis or metastases. Patients without an event will be censored at the last date the patient was known to be disease-free.

Inclusion Criteria: Rectal cancer patients, clinically staged as T2-T3 by MRI or endoscopic/trans-rectal ultrasound Rectal cancer staged as N0 by MRI or EUS/TRUS No metastatic lesion Rectal tumor occupying less than half of the circumference Tumor less than 5 cm on its largest dimension Tumor located at less than 10 cm from the anal verge Tumor penetration less than 5 mm in the mesorectal fat Tumor accessible for brachytherapy Lumen accessible for colonoscopy Patient should be a suitable candidate for brachytherapy and chemotherapy Older than 18 years of age Adequate birth control measures in women of childbearing potential Written informed consent Exclusion Criteria: Patients with previous pelvic radiation Evidence of distant metastasis Extension of malignant disease to the anal canal Tumors staged as T4 Tumors larger than 5 cm in length